Influence of admixed lactose on pelanserin hydrochloride release from hydroxypropyl methylcellulose matrix tablets

Pelanserin, a weakly basic experimental drug with a short half-life, was taken as a model to study the influence of lactose on hydroxypropyl methylcellulose matrices to modulate a gradual release. Powder mixtures were wet-granulated with water and compressed in a hydraulic press at 55 MPa. Dissolution media were 900 ml HCl 0.1 N, the first 3 h and phosphate buffer pH 7.4, 3 to 8 h. Dissolution curves were described by M(t)/M(inf)=kt(n), applied separately for each dissolution medium. Dissolution mechanism involved diffusion/relaxation with a linear trend favoring the diffusion mechanism with increasing lactose concentrations. Increasing lactose concentrations produced higher kinetic constants, in a cubic relationship. A double HPMC proportion produced slower dissolution rates, with a more gradual lactose release but including certain degree of erosion. High lactose concentrations compensated for a decreased solubility of pelanserin at pH 7.4. Copyright (C) 1999 Elsevier Science B.V.